Cancers are diseases of uncontrolled proliferation of abnormal cells. Urothelial carcinoma of the urinary bladder represents more than 90% of all bladder cancers, about 80% of which are non-muscle invasive bladder cancer (NMIBC), a form of superficial cancer. Transurethral resection and radical cystectomy remain the mainstay of treatment for NMIBC and MIBC (muscle invasive bladder cancer), respectively. Intravesical therapy of Bacillus calmette-Guerin (BCG) and mitomycin are preferable adjuvant therapies to surgery aiming at reducing disease recurrence and progression. The major drawback for intravesical instillation is the short exposure time of tissue to the drug due to urine creation and voiding that dilutes and displaces drug from the area of treatment.
It is well known that malignant neoplasms consist of heterogeneous cells which proliferate asynchronously. As a result, administered cytotoxic drugs will affect only those malignant cells that are at the specific cell cycle phase at which the drug is most efficacious. The rest of the cells will be affected only if the exposure time is long enough to permit the cells to cycle to the phase sensitive to the specific chemotherapeutic drug. In the bladder and other body cavities of continual secretion and voiding, exposure time of a cancer target to cytotoxic drugs will be limited. Therefore, the treatment efficiency will be relatively low and will require repeating treatment sessions.
Thus there remains a need for improvements in delivery and efficacy of non-surgical cancer treatments of cancers in secreting and voiding areas of the body such as the urinary tract, and particularly the bladder.
The present invention therefore seeks to provide new combinations of cell cycle regulators and at least one anti-cancer agent for the treatment of proliferative disorders, especially cancer. More specifically, the invention relates to unexpected effects associated with increased efficacy for treating cancer while using cell cycle modifiers and at least one anti-cancer agent, each embedded in a thermoreversible hydrogel matrix and locally administered to the affected body cavity, such as by intravesical means.